Project Summary Uveitis accounts for as much acquired visual loss as diabetes or macular degeneration. Although many entities cause uveitis, the most frequent diagnosis is ?idiopathic?, a description that frustrates patients and physicians. We have shown that some systemic diseases associated with uveitis demonstrate distinct gene expression profiles that can be identified in blood. We propose to characterize the gene expression profile for 4 important causes of uveitis: sarcoidosis, ankylosing spondylitis, inflammatory bowel disease, and tubulointerstitial nephritis with uveitis. Our study will determine if the profiles for each disease have adequate sensitivity and specificity to become diagnostic tools. We will test the hypothesis that many diseases that cause uveitis share expression of common RNA transcripts. We will segregate subjects with idiopathic uveitis on the basis of gene expression and validate this classification by determining if the clinical phenotype of the uveitis fits with the gene expression profile. By studying subjects longitudinally over the course of the proposal, we will distinguish transcripts that are indicative of the disease phenotype in contrast to transcripts that are indicative of the disease activity. The proposed studies represent a potential paradigm shift in the approach to uveitis and a prime example of the application of precision medicine to a clinical conundrum.